Based on explicit models of pathogenesis for TS and OCD, an array of clinical neuropsychological, genetic, neurobiological and neuroimaging techniques have been selected. A major focus of the program project involves a detailed study of 440 probands, aged 7 to 50 years, and their first degree family members drawn from a regional referral base. All probands will be studied using clinical, neuropsychological, genetic, neurobiological and neuroimaging techniques. Subsets of these probands will also participate in a clinical trial and/or a CSF study. In addition, a sample of 200 affected sib pairs (TS=100 and OCD=100) and a set of ten large multigenerational kindreds (TS=5,OCD=5) will be selected from a larger referral base for genetic linkage and association studies. A series of interrelated neuropathological studies are also proposed using postmortem brain tissue from more than 20 TS patients and more than 40 controls. These studies are divided into four projects and are supported by three cores.